My major long term research objective is concerned with the nutritional significance of selenium. The objective of the present study is to examine the relationship of selenium to two proteins. Selenium has been shown to be present in several proteins. It has been shown that selenium is important in preventing mercury toxicity. Data are presented which indicate that this effect may be mediated through the binding of selenium and mercury to a specific plasma protein. Part of this proposal is designed to study the nature of the binding in this specific selenium-mercury-containing protein in rat plasma and to assess its physiological significance. The other part of the proposal is designed to study the physiological role of selenium in the hepatic microsomal drug-metabolizing system. Preliminary evidence demonstrating failure of cytochrome P-450 induction to phenobarbital in selenium deficiency is presented. This enzyme system is important in the metabolism of many drugs as well as pesticides and naturally-occurring substances. Selenium deficiency is widespread among animals in many areas of the United States and could cause increased susceptibility to environmental contaminants normally metabolized by this system.